The skin of all living things grows aged as it grows older. In order to delay this skin aging, many efforts have been made extensively. As a result, the questions on the essence and cause of the aging have always been raised. Skin aging is classified into two kinds depending on its cause. The first is intrinsic aging that the structure of and the physiological function of the skin decline successively as aging goes on. And, the second is extrinsic aging that is caused by accumulated stress such as UV radiation. Particularly, UV radiation is well-known cause of aging. In case of the skin exposed to UV radiation for a long time, stratum corneum of the skin becomes thicker and collagen and elastin, which are main components of the skin, get denatured so that skin loses its elasticity. Thus, skin aging is accompanied by several functional and structural changes.
As structural changes caused by skin aging, epidermis, dermis and hypoderm of the skin become thinner. And, dermal ECM (extracelluar matrix), which is in charge of skin elasticity and elongation, is experienced with its component's change. ECM is composed of two components, i.e. elastic fiber which amounts to 2˜4% of total ECM and collagen which amounts to 70˜80%. As skin aging goes on, the skin loses elasticity due to the reduction of collagen and elastin. These reductions are caused by several factors in biosynthesis. For example, matrix metallo proteases, such as collagenase and elastase, are expressed to decompose collagen and elastin, and the collagen content within the skin is reduced. The reduction of collagen and elastin within the dermis leads the epidermis to be rough and to lose elasticity. That is, the skin becomes aged.
In order to suppress the reductions of collagen and elastin, which are a cause of the skin elasticity reduction, some materials have been developed and used. Specially, retinoid such as retinol and retinoic acid has been known to be very effective in lessening skin wrinkles and improving skin elasticity (Dermatology therapy, 1998, 16, 357˜364). In spite of its anti-wrinkle efficacy and elasticity-improving efficacy, retinoid has some drawbacks that only a small quantity of application causes irritation to the skin and is easily oxidized in an air due to its instability, thus there are lots of limitation in using it. In order to stabilize retinoid, many studies have been conducted. However, the irritation of retinoid onto the skin, that is troubles in safety onto the skin, remains unsolved.
Retinoid includes retinol, retinoic acid or its derivatives. It exhibits various biological activities. With regard to the skin, the efficacy on abnormal keratinization or on pimple was reported. And, with regard to the skin wrinkles, it has been known that it can promote collagen biosynthesis and inhibit the activity of collagenase, i.e. an enzyme for decomposing collagen (The Journal of Investigative Dermatology, 1991, 96, 975˜978). In addition, retinoid can inhibit the expression of elastase, with regard to the elasticity-reduction.
Up to now, retinoid has been developed as follows:
In the first stage, simple derivatives of retinol or retinoic acid were developed. As a derivative, retinyl palmitate may be exemplified. In the next, retinoid derivative including benzoic acid was developed. This derivative is named as arotinoid (J. Med. Chem, 1988, 31, 2182˜2192). Recently, compounds including heteroatom introduced into the benzene ring of arotinoid, called as heteroarotinoid, have been developed (J. Med. Chem., 1999, 42, 4434˜4445).
Retinoid was reported to exhibit biological efficacy on the skin by interacting with the intercellullar receptor called as retinoic acid receptor (British Journal of dermatology, 1999, 140, 12˜17). The structural feature of retinoid is based on tetramethyl cyclohexane, unsaturated carbon bond and carboxylic acid. Specially, carboxylic acid moiety is essential in the action of retionids and can be easily converted into an anion when interacting with the receptor (Chem. Pharm. Bull, 2001, 49, 501˜503).
Arotinoid includes benzoic acid substituted for carboxylic acid moiety of retinoic acid. Benzoic acid moiety can be easily ionized to act as an anion. Recent studies have synthesized derivatives including various substituents for carboxylic acid moiety. These substituent-conversions are in order to maintain original efficacy of retinoid and to lessen toxicity or irritation and instability thereof. For the purpose, many studies have been conducted.